Kidney Structure Research Articles

PECULIARITIES OF SOURCES OF RUDIMENTS AND MORPHOGENESIS OF THE PELVICALYCEAL SYSTEM OF THE KIDNEY IN EARLY PERIOD OF THE HUMAN PRENATAL ONTOGENESIS

The aim of the study – to determine the peculiarities of the rudiments sources and thechronological sequence of topographical and anatomical transformations of the organsand structures of the human urinary system.Materials and methods. The material for the study was 14 series of consecutivehistological sections of specimens of human embryos and prefetuses (4.0-66.0 mm parietalcoccygeal length (PCL)) aged from 4th to 11th weeks of intrauterine development (IUD) A complex of modern methods of morphological research (anthropometry, morphometry,microscopy, 3D computer reconstruction, statistical analysis) were applied.The results. The first signs of mesonephric duct diverticula formation are determined inhuman embryos of the 5th week of the IUD (embryos 7.0-7.5 mm PCL). It is represented byan ampoule-like blind expansion of the diverticulum – the primary rudiment of the renalpelvis, which is surrounded by a condensed mesenchyme, that is the formation sourceof the renal parenchyma – a nephrogenic blastema. Starting from the embryos of themiddle of the 5th week of IUD, due to 3D computer reconstruction, the first topographicaland anatomical features of the primordia of the structures of the definitive kidney aredetermined. The rudiments of the renal pelvises – paired ampoule-like blind expansionsof the diverticulum of the mesonephric duct – are immersed in the metanephric blastema,which has the shape of a drop due to the upper narrowed end. Starting from the end of the6th week of IUD, there is a evagination of the wall of the blind end of the diverticulum (therudiment of the renal pelvis) in the cranial and caudal directions, i.e., the rudiments ofmajor calyces appears. The rudiments of the minor cups is formed by the evagination ofthe wall of the major calices and appears in prefetuses at the beginning of the 7th week ofIUD. Age-related topographical and anatomical changes of the kidneys were also traced.Conclusions. 1. On the specimens of embryos 4.7-5.5 mm PCL (4th week of IUD),mesodermal sources of rudiments of structures and organs of the genitourinary system,which originate from the paired genitourinary crest, are determined. At the border of thedorsal and ventral parts of the mesoderm, in the intermediate mesoderm, the source of theurinary tubules is carried out, which form the nephrogenic cord – the only source of layingof all three generations of the kidney. At the end of the 4th week of IUD, an evaginationappears on both sides from the dorsal wall of the excretory duct of the mesonephros in itscaudal part, which is the rudiment of the epithelial lining of the ureter and renal pelvis.2. The rudiment of the renal pelvis is observed for the first time in the 5th week of IUD(embryos 7.0-7.5 mm PCL), major cups – at the end of the 6th week of VUR (embryos12.0-13.5 mm TKD), small calices – at the beginning of the 7th week of IUD (prefetuses14.0-15.0 mm PCL). 3. In the process of intrauterine development, the kidneys move fromtheir original location in the pelvis, where the source of their blood supply is the commoniliac artery, cranial to the primordia of the adrenal glands, giving their own vessels to theaorta, which become renal arteries.

Sufentanil promotes autophagy and improves ischemia-reperfusion-induced acute kidney injury via up-regulating microRNA-145.

Sufentanil has a good protective effect on myocardial and liver injury caused by ischemia reperfusion (IR), but its protective effect on kidney is still unclear. This study aims to investigate whether sufentanil can prevent IR-induced acute kidney injury (AKI) and to determine whether its efficacy is related to miR-145-mediated autophagy. A total of 40 rats were randomly divided into 5 groups (n=8 in each group): A sham group, an IR group, a sufentanil group, a sufentanil+miR-145 inhibitor control group (an anti-NC group) and a sufentanil+miR-145 inhibitor group (an anti-miR-145 group). Except for the sham group, the other groups established a rat AKI model induced by IR. The sufentanil group, the sufentanil+anti-NC group, and the sufentanil+anti-miR-145 were injected with sufentanil (1 μg/kg) through femoral vein 30 min before ischemia. The sufentanil+anti-NC group and the sufentanil+anti-miR-145 group were injected with miR-145 inhibitor control or anti-miR-145 (80 mg/kg) through the tail vein before sufentanil pretreatment. The structure and function of kidneys harvested from the rats were evaluated, and the protein levels of autophagy-related proteins, oxidative stress levels, and apoptosis levels were measured. Compared with the IR group, the renal structure and function were improved in the sufentanil group. The levels of blood urea nitrogen (BUN), creatinine (Cr), urinary kidney injury molecule 1 (KIM-1), neutrophil gelatinase related lipid transporter (NGAL), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and ROS were significantly decreased (all P<0.05). In addition, compared with the IR group, the levels of Beclin-1 and LC3 in renal tissues in the sufentanil group were significantly increased (both P<0.05), and the apoptosis in renal tissues was significantly reduced (P<0.05). Compared with the sufentanil+anti-NC group, the levels of BUN, Cr, KIM-1, NGAL, TNF-α, IL-1β, IL-6 and ROS in the sufentanil+anti-miR-145 group were significantly increased (all P<0.05), the levels of Beclin-1 and LC3 in renal tissues were significantly decreased (both P<0.05), and the apoptosis in renal tissues was significantly increased (P<0.05). Sufentanil can prevent the AKI induced by IR, which is related to the up-regulation of miR-145-mediated autophagy.

Translating Organoids into Artificial Kidneys.

Purpose of Review Kidney disease affects more than 13% of the world population, and current treatment options are limited to dialysis and organ transplantation. The generation of kidney organoids from human-induced pluripotent stem (hiPS) cells could be harnessed to engineer artificial organs and help overcome the challenges associated with the limited supply of transplantable kidneys. The purpose of this article is to review the progress in kidney organoid generation and transplantation and highlight some existing challenges in the field. We also examined possible improvements that could help realize the potential of organoids as artificial organs or alternatives for kidney transplantation therapy.Recent FindingsOrganoids are useful for understanding the mechanisms of kidney development, and they provide robust platforms for drug screening, disease modeling, and generation of tissues for organ replacement therapies. Efforts to design organoids rely on the ability of cells to self-assemble and pattern themselves into recognizable tissues. While existing protocols for generating organoids result in multicellular structures reminiscent of the developing kidney, many do not yet fully recapitulate the complex cellular composition, structure, and functions of the intact kidney. Recent advances toward achieving these goals include identifying cell culture conditions that produce organoids with improved vasculature and cell maturation and functional states. Still, additional improvements are needed to enhance tissue patterning, specialization, and function, and avoid tumorigenicity after transplantation.SummaryThis report focuses on kidney organoid studies, advancements and limitations, and future directions for improvements towards transplantation.

A single short reprogramming early in life initiates and propagates an epigenetically related mechanism improving fitness and promoting an increased healthy lifespan.

Recent advances in cell reprogramming showed that OSKM induction is able to improve cell physiology in vitro and in vivo. Here, we show that a single short reprogramming induction is sufficient to prevent musculoskeletal functions deterioration of mice, when applied in early life. In addition, in old age, treated mice have improved tissue structures in kidney, spleen, skin, and lung, with an increased lifespan of 15% associated with organ-specific differential age-related DNA methylation signatures rejuvenated by the treatment. Altogether, our results indicate that a single short reprogramming early in life might initiate and propagate an epigenetically related mechanism to promote a healthy lifespan.

Gut-Kidney Impairment Process of Adenine Combined with Folium sennae-Induced Diarrhea: Association with Interactions between Lactobacillus intestinalis, Bacteroides acidifaciens and Acetic Acid, Inflammation, and Kidney Function.

Background: Extensive evidence suggests that gut microbiota may interact with the kidneys and play central roles in the pathogenesis of disease. However, the association of gut microbiota-kidneys in diarrhea remains unclear. Methods: A diarrhea mouse model was constructed by combining adenine with Folium sennae. We analyzed the characteristics of the gut content microbiota and short chain fatty acids (SCFAs); and explored the potential link between gut content microbiota, SCFAs, intestinal inflammatory response and kidney function. Results: Characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens were enriched in the gut contents of mice. The productions of SCFAs were remarkably inhibited. Model mice presented an increased trend of creatinine (Cr), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), a decreased trend of blood urea nitrogen (BUN) and secretory immunoglobulin A (SIgA). The pathological analysis proved obvious damage to the kidney structure. Lactobacillus intestinalis and Bacteroides acidifaciens exisited in the correlations with acetic acid, intestinal inflammatory response and kidney function. Conclusions: Adenine combined with Folium sennae-induced diarrhea, altered the structure and function of the gut content microbiota in mice, causing the enrichment of the characteristic bacteria Lactobacillus intestinalis and Bacteroides acidifaciens. The interactions between Lactobacillus intestinalis, Bacteroides acidifaciens and acetic acid, intestinal inflammation, and kidney function might be involved in the process of gut-kidney impairment in adenine, combined with Folium sennae-induced diarrhea.

Photothermal effects of CuS-BSA nanoparticles on H22 hepatoma-bearing mice.

The objective of this study was to evaluate the in vivo application and photothermal ablation effects and mechanism of copper sulfide nanoparticles (CuS NPs) in hepatocellular carcinoma (HCC). Sheet-like CuS-BSA NPs with a particle size of 30 nm were synthesized using bovine serum albumin (BSA) as a biological modifier, and were physically characterized. To provide a reference range for the biosafety dose of CuS-BSA NPs, 36 male Kunming mice were randomly assigned into six groups. Different one-time doses of CuS-BSA NPs were injected via tail vein injection, and the potential damages of liver, kidney and spleen were observed 14 days later. To evaluate the in vivo photothermal effect of CuS-BSA NPs, 48 male Kunming mice were used to establish the H22 hepatoma-bearing mouse model and were randomly assigned into six groups. CuS-BSA NPs (600 μg/kg) were injected via tail vein or intratumoral injection. Irradiations were performed 30 min after injection, with a 980 nm near-infrared laser (2.0 W/cm2) for 10 min once a week for 3 weeks. The results indicated that the CuS-BSA NPs had good dispersibility in three different solvents and had a strong absorption peak at 980 nm. The heating curves demonstrated that the photothermal effects of CuS-BSA NPs aqueous solution exhibited concentration dependence and power density dependence. In the in vivo experiment, when the doses of CuS-BSA NPs were in the range of 1800–7,200 μg/kg, the thymus index and spleen index of mice were not significantly different from those of the control group, and the structures of liver, kidney and spleen were intact without remarkable pathological changes. A lower dose of CuS-BSA NPs (600 μg/kg) could effectively inhibit tumor growth in H22 hepatoma-bearing mice at 980 nm NIR. Moreover, under the near-infrared laser irradiation, both in the tail vein injection group and the intratumoral injection group, a large area of necrosis in the tumor tissue, as well as the up-regulation of apoptotic proteins including cleaved caspase-3 and cleaved caspase-9 were observed. CuS-BSA NPs are promising photothermal agents in the photothermal therapy of cancer.

The centrosomal protein 83 (CEP83) regulates human pluripotent stem cell differentiation toward the kidney lineage.

During embryonic development, the mesoderm undergoes patterning into diverse lineages including axial, paraxial, and lateral plate mesoderm (LPM). Within the LPM, the so-called intermediate mesoderm (IM) forms kidney and urogenital tract progenitor cells, while the remaining LPM forms cardiovascular, hematopoietic, mesothelial, and additional progenitor cells. The signals that regulate these early lineage decisions are incompletely understood. Here, we found that the centrosomal protein 83 (CEP83), a centriolar component necessary for primary cilia formation and mutated in pediatric kidney disease, influences the differentiation of human-induced pluripotent stem cells (hiPSCs) toward IM. We induced inactivating deletions of <i>CEP83</i> in hiPSCs and applied a 7-day in vitro protocol of IM kidney progenitor differentiation, based on timed application of WNT and FGF agonists. We characterized induced mesodermal cell populations using single-cell and bulk transcriptomics and tested their ability to form kidney structures in subsequent organoid culture. While hiPSCs with homozygous <i>CEP83</i> inactivation were normal regarding morphology and transcriptome, their induced differentiation into IM progenitor cells was perturbed. Mesodermal cells induced after 7 days of monolayer culture of <i>CEP83</i>-deficient hiPCS exhibited absent or elongated primary cilia, displayed decreased expression of critical IM genes (<i>PAX8</i>, <i>EYA1</i>, <i>HOXB7</i>), and an aberrant induction of LPM markers (e.g. <i>FOXF1</i>, <i>FOXF2</i>, <i>FENDRR</i>, <i>HAND1</i>, <i>HAND2</i>). Upon subsequent organoid culture, wildtype cells differentiated to form kidney tubules and glomerular-like structures, whereas <i>CEP83</i>-deficient cells failed to generate kidney cell types, instead upregulating cardiomyocyte, vascular, and more general LPM progenitor markers. Our data suggest that <i>CEP83</i> regulates the balance of IM and LPM formation from human pluripotent stem cells, identifying a potential link between centriolar or ciliary function and mesodermal lineage induction.

Diarrhea with deficiency kidney-yang syndrome caused by adenine combined with Folium senna was associated with gut mucosal microbiota.

The present study aims to study and analyze the characteristics of gut mucosal microbiota in diarrhea mice with deficiency kidney-yang syndrome. Ten male mice were randomly divided into the control group and the model group. Diarrhea mice model with deficiency kidney-yang syndrome was established by adenine combined with Folium sennae. The kidney structure was observed by hematoxylin-eosin (HE) staining. Serum Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase were detected by enzyme-linked immunosorbent assay (ELISA). The characteristics of gut mucosal microbiota were analyzed by performing third-generation high-throughput sequencing. The results showed that the model mice exhibit obvious structural damage to the kidney. Serum Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase levels showed a decreased trend in the model group. The diversity and community structure of the gut mucosal microbiota improved in the model group. Dominant bacteria like Candidatus Arthromitus, Muribaculum, and Lactobacillus reuteri varied significantly at different taxonomic levels. The characteristic bacteria like Bacteroides, Erysipelatoclostridium, Anaerotignum, Akkermansia muciniphila, Clostridium cocleatum, Bacteroides vulgatus, and Bacteroides sartorii were enriched in the model group. A correlation analysis described that Erysipelatoclostridium was positively correlated with Na+-K+-ATP-ase and Ca2+-Mg2+-ATP-ase levels, while Anaerotignum exhibited an opposite trend. Together, adenine combined with Folium sennae damaged the structure of the kidney, affected energy metabolism, and caused disorders of gut mucosal microbiota in mice. Bacteroides, Erysipelatoclostridium, and Anaerotignum showed significant inhibition or promotion effects on energy metabolism. Besides, Akkermansia muciniphila, Clostridium cocleatum, Bacteroides vulgatus, and Bacteroides sartorii might be the characteristic species of gut mucosal microbiota responsible for causing diarrhea with deficiency kidney-yang syndrome.

PERSISTENT ALBUMINURIA IN A LARGE PROSPECTIVE COHORT OF CHILDREN WITH SICKLE CELL ANEMIA: RATES AND RISK FACTORS

Sickle Cell Anemia (SCA) modifies kidney structure and function. Progressive reduction in kidney function begins at very young stages of life with abnormally increased glomerular filtration rate, followed by albuminuria in late childhood. Albuminuria has been associated with poor prognosis. However, albuminuria is often intermittent in individuals with SCA, and its progression over time needs to be better understood. We aimed to investigate the progression of albuminuria and its risk factors in a large prospective cohort of children with SCA. We recruited steady-state pediatric patients with SCA at ‘Fundação Hemominas'outpatient clinic, Minas Gerais, Brazil. Random-spot urine specimens were collected during routine visits. Albuminuria was defined by urinary albumin/creatinine ratio ≥30 mg/g of creatinine. Participants were prospectively categorized by the presence or absence of albuminuria at baseline and on the follow-up urine test. Participants with albuminuria at baseline and on the follow-up urine test were considered to have persistent albuminuria. Those with no albuminuria at baseline or on the follow-up urine tests were considered to have no albuminuria. Participants with no albuminuria at baseline who developed albuminuria on the follow-up test were considered progressors. Those with albuminuria at baseline but none on follow-up were considered remitters. Baseline steady-state laboratory data were obtained from medical records. Baseline kidney injury biomarkers in urine were measured using multilplex xMAP® assays. Univariate and multivariate analyses were performed using Cox regression. From 572 children included in the cohort [287 (50.2%) males], 112 (19.6%; 95% CI:16.3%–22.8%) had albuminuria at enrollment; mean age was 12.9±4.6 years. A total of 246 participants (43%) had two samples and were included in the longitudinal analysis. The median follow-up was 2.1 (6m–4y) years, providing 467.9 patient-years. One hundred eight-seven (76%) participants were receiving intensification therapy (HU, chronic blood transfusion, or both). Out of 246 participants, 169 (68.7%) presented no albuminuria, 13 (5.3%) were progressors, 19 (7.7%) remitters, and 45 (18.3%; 95% CI 13.5%–23.1%) had persistent albuminuria. The incidence of persistent albuminuria was 9.6/100 patient-years (95% CI 6.9–12.3). In cox multivariate analysis, persistent albuminuria was associated with older age (HR = 1.1, 95% CI 1.02–1.19; p = 0.018), lower total Hb (HR = 0.75, 95% CI 0.57–0.98; p = 0.040), and higher indirect bilirubin (HR = 1.3, 95% CI 1.11–1.58; p = 0.002) and kidney injury molecule-1 levels (HR = 1.007, 95% CI 1.001–1.013; p = 0.020). This study provides important findings on the natural history of albuminuria during childhood of individuals with SCA. The prevalence of persistent albuminuria was similar to previously published studies in children with SCA (13% to 30%). Our findings replicated the association of persistent albuminuria with aging, anemia, and higher levels of hemolysis and renal tubular injury markers. These features may allow early identification of individuals at highest risk for persistent albuminuria, enabling therapeutic interventions to prevent the decline of renal function. This study showed a high frequency of persistent albuminuria in children with SCA. Age, anemia, and biomarkers of hemolysis and renal tubular injury were significantly associated with persistent albuminuria.

Nephroprotective effect of the hydromethanolic extract and fractions of Viola serpens Wall. Histological and hematological evidence

The current study was planned to examine the nephroprotective effect of the crude extract and its various fractions of Viola serpense Wall against paracetamol-induced toxicity in rabbits. The serum creatinine levels of all fractions, as well as the crude extract, were found to have a greater effect. The effect on urine urea by the n-hexane, ethyl acetate, n-butanol and aqueous fraction in high doses (300 mg/kg b.wt.) and crude extract and chloroform in low doses (150 mg/kg bwts.) were comparatively more effective and comparable to silymarin. The creatinine clearance of the fractions except for chloroform, aqueous at 300 mg/kg and the hydro-methanolic extracts at both doses were highly significant. The histological structures of kidneys in crude extract and chloroform-treated groups showed more improvement at the lower doses. The fractions n-hexane, ethyl acetate and n-butanolic exhibited an inverse dose relationship in the histology of the kidney. However, the aqueous fraction showed a dose-dependent nephroprotective effect. Finally, the crude extract and fractions significantly improved paracetamol-induced nephrotoxicity in rabbits.

Nomenclature for kidney function and kidney diseases - Improving assessment and prognosis through precision and comprehensibility

ZusammenfassungNierenkrankheiten stellen ein zunehmendes Gesundheitsproblem dar, dessen Eindämmung eine effektive Kommunikation zwischen den an Erfassung, Diagnostik und Therapie Beteiligten sowie den betroffenen Patientinnen und Patienten erfordert. Die Nomenklatur für Nierenfunktion und Nierenkrankheiten ist jedoch bislang nicht einheitlich. Die internationale, gemeinnützige Organisation Kidney Disease: Improving Global Outcomes (KDIGO) hat deshalb 2019 in einem Konsensus-Prozess ein englischsprachiges Glossar entwickelt, um die Begriffe zur Beschreibung von Nierenfunktion, Nierenstruktur und Nierenkrankheiten zu vereinheitlichen. Leitprinzipien bei der Entwicklung dieser Nomenklatur waren (1) Präzision, (2) Patientenzentrierung und (3) Konsistenz mit bisherigen KDIGO-Leitlinien. Das vorliegende Positionspapier beinhaltet eine deutsche Übersetzung dieses Glossars, die im Auftrag der nephrologischen Fachgesellschaften in Deutschland, Österreich und der Schweiz entwickelt wurde.

Role of Oral Supplementation of Damiana (Turnera diffusa) Reduces the Renal Toxicity, Apoptosis and DNA Damage Associated with Amitriptyline Administration in Rats

Major depressive disorder and anxiety disorders are two mental diseases that are treated with amitriptyline (AMT). AMT treatments induced liver, heart and testes toxicity; As a result, the purpose of this study was to determine the preventative and therapeutic role of damiana (Dam) as adjuvant herbal therapy against AMT induced heart injury in rats. Six groups of 36 rats (male albino) were randomly assigned; first one is control, second is Dam, third was AMT, fourth was Dam+AMT, fifth was AMT+Dam and sixth was AMT self-healing. A significant elevation in creatinine, urea, sodium (Na+), Chloride (Cl+), renal injury, DNA damage and apoptosis in treatment rats with amitriptyline and self-healing group as related to control and damiana groups. Conversely; potassium (K+) and calcium (Ca++) were a significant decrease in AMT and self-healing groups as compared with control. Treatment of AMT with Dam (Co and Post) revealed a modulation and improvement of renal toxicity with best result in co- treatments than post treatments. As a result, AMT treatments encouraged changes in kidney functions and structure and the post-treatments of AMT with dam modulates these alterations.

The Role of Urinary Potassium Examination on the Progressivity of Chronic Kidney Disease: A Narrative Literature Review

Kidneys play an important role in potassium homeostasis. The important role of the kidneys in maintaining potassium balance is reflected in the high level of potassium disturbances in patients with decreased kidney function, especially patients with severely decreased renal function and patients who have comorbidities, such as diabetes, hypertension, or heart failure. Chronic kidney disease is characterized by abnormalities of kidney structure or function that persist for more than 3 months, have many complex causes, and have a major impact on global health status. There are several methods to measure the amount of potassium intake consumed, including a food frequency questionnaire, dietary recall, temporary urine potassium examination, and 24-hour urine potassium examination. The standard gold measurement for evaluating urinary potassium excretion is through 24-hour urine collection. This literature review aims to describe the role of urinary potassium excretion in assessing the progression of chronic kidney disease.

Thyroid Function Abnormalities in Patients with Different Stages of Chronic Kidney Disease

Introduction: Thyroid hormones are crucial for renal development and physiology. Thyroidal hormones affect the cardiovascular system through their influence on renal blood flow as it modulates the glomerular function, the tubular secretory and absorptive capacities as well as the electrolyte pumps and the kidney structure. Objective: To assess the thyroid function abnormalities in patients with different stages of chronic kidney disease. Materials and Methods: The cross sectional observation study was conducted in Department of Medicine, 250 Bed District Hospital, Habiganj, Bangladesh from January to April 2021. Included 54 CKD patients not on dialysis, who are only on conservative management. Results: In our study the age matched graph shows that maximum number of patients in the category of 40-49 years with 8 males and 6 females, 50- 59 years had 8 males and 6 females, whereas between 60 to 69 years there were 6 males and 6 females. The extreme age groups had few patients chronic kidney disease above 70 there were 2 females and 2 males between 18-29 years there were 3 males and 3 females and 30-39 years had 1 male and 3 females. In our study the number of chronic kidney patients having low T3 were 39 which constitutes 72.2%,the patients with normal T3 were 12 constituting 22.2% and those with high T3 were 3, suggesting primary hyperthyroidism, so excluding them 75% of our patients had low T3 syndrome. In our study 39 patients had low T3, 26 had low T4 with 49 patients being normal TSH, only 4 had high high TSH. Excluding patients with primary hypothyroidism. Patients with low T3 low T4 were clustered in more towards end stage renal disease with 60%. Patients also were in moderate number with low T3 and low T4 in stage 4 chronic kidney disease. 20% in stage 3 chronic kidney disease T4 and TSH were almost normal with only 10% patients had low T3 syndrome. In stage 2 chronic kidney disease 10% had low T3, low T4 with rest being normal TSH. In our study patients .....

Spatially resolved whole transcriptome profiling in human and mouse tissue using Digital Spatial Profiling.

Emerging spatial profiling technology has enabled high-plex molecular profiling in biological tissues, preserving the spatial and morphological context of gene expression. Here, we describe expanding the chemistry for the Digital Spatial Profiling platform to quantify whole transcriptomes in human and mouse tissues using a wide range of spatial profiling strategies and sample types. We designed multiplexed in situ hybridization probes targeting the protein-coding genes of the human and mouse transcriptomes, referred to as the human or mouse Whole Transcriptome Atlas (WTA). Human and mouse WTAs were validated in cell lines for concordance with orthogonal gene expression profiling methods in regions ranging from ∼10-500 cells. By benchmarking against bulk RNA-seq and fluorescence in situ hybridization, we show robust transcript detection down to ∼100 transcripts per region. To assess the performance of WTA across tissue and sample types, we applied WTA to biological questions in cancer, molecular pathology, and developmental biology. Spatial profiling with WTA detected expected gene expression differences between tumor and tumor microenvironment, identified disease-specific gene expression heterogeneity in histological structures of the human kidney, and comprehensively mapped transcriptional programs in anatomical substructures of nine organs in the developing mouse embryo. Digital Spatial Profiling technology with the WTA assays provides a flexible method for spatial whole transcriptome profiling applicable to diverse tissue types and biological contexts.

Resveratrol improved kidney function and structure in malignantly hypertensive rats by restoration of antioxidant capacity and nitric oxide bioavailability

The main cause of death among patients with malignant hypertension is a kidney failure. The promising field in essential and malignant hypertension therapy could be centered on the amelioration of oxidative stress using antioxidant molecules like resveratrol. Resveratrol is a potent antioxidative agent naturally occurred in many plants that possess health-promoting properties. In the present study, we investigated the therapeutic potential of resveratrol, a polyphenol with anti-oxidative activity, in NG-L-Arginine Methyl Ester (L-NAME) treated spontaneously hypertensive rats (SHR) - malignantly hypertensive rats (MHR). Resveratrol significantly improves oxidative damages by modulation of antioxidant enzymes and suppression of prooxidant factors in the kidney tissue of MHR. Enhanced antioxidant defense in the kidney improves renal function and ameliorates the morphological changes in this target organ. Besides, protective properties of resveratrol are followed by the restoration of the nitrogen oxide (NO) pathway. 4) Conclusion: Antioxidant therapy with resveratrol could represent promising therapeutical approach in hypertension, especially malignant, against kidney damage.

Exosomes from adipose-derived stem cells inhibit inflammation and oxidative stress in LPS-acute kidney injury

Acute renal damage presents a significant danger to kidney health. Previous research has found that acute kidney injury shows high levels of oxidative stress and inflammation caused by sepsis. Although mesenchymal stem cells (MSCs) can repair acute kidney injury. However, involvement of MSCs exosomes generated from adipose tissue and bone marrow in lipopolysaccharide-induced acute kidney damage is not clear. LPS (7.5 mg/kg) intraperitoneal injection was used to produce AKI, and 30 min before the LPS administration, adipose-derived MSCs (ADSCs) exosomes (1 × 105 and 5 × 105) and bone marrow-derived MSCs(BMSCs) exosomes (1 × 105 and 5 × 105) were delivered individually. The function of the rat kidney was explored. Inflammation, oxidative stress, and autophagy levels were further investigated. Both adipose-derived and bone marrow-derived MSCs can enhance renal function and structural damage, such as BUN, Creatinine, and cystatin C levels, as well as tubular damage scores. These findings indicate that both adipose-derived MSCs exosomes and bone marrow-derived MSCs exosomes decrease oxidative stress and inflammation, as well as make a substantial influence on kidney tissue in autophagy levels. Furthermore, compared to bone marrow-derived MSCs exosomes, adipose-derived MSCs exosomes improved kidney function and structure more significantly. We discovered that adipose-derived MSCs exosomes protect against LPS-induced AKI by inhibiting oxidative stress and inflammation.

Incidental Findings on Computerized Tomography Images of Trauma Cases.

This study aimed to evaluate the characteristics of incidental findings (IFs) on computed tomography (CT) scans of trauma admissions, examine associations between IFs and gender and age-groups, and discuss the management strategies. The CT reports were retrospectively reviewed to evaluate IFs. Cases were divided into five age-groups (0-19, 20- 39, 40-59, 60-79,≥80). IFs were classified as "Group 1": congenital anomalies that do not require further investigation, non-degenerative/minor degenerative findings; "Group 2": findings that do not require immediate intervention, require outpatient follow-up/in case of symptoms; and "Group 3": findings that require immediate intervention/further investigation. There were 2385 CT scans and 1802 incidental findings (IFs) in 783 trauma cases. CT scans with IFs constituted 50.2%. The percentage of IFs was 75.6% in males and 24.4% in females, and they occurred in 4.8%, 27.6%, 44.3%, 20.9%, and 2.4% of age groups 1 to 5, respectively. Group 1 had 34.6%, group 2 had 54.6%, and group 3 had 10.8% IFs. There was not any significant association between the classification and gender or age-groups. In terms of organs, IFs of the thyroid and gall bladder & bile ducts were significantly higher among females (P=0.044 and P<0.001, respectively), while IFs in the head & neck region were significantly higher in males (P<0.001). Incidental findings in the kidney, liver, adrenal gland, and vascular structures differed significantly across age-groups (P<0.05). There were no significant relationships between the classification of IFs and gender or age-groups. However, the distribution of IFs was significantly associated with gender and age-groups in terms of organs. Healthcare professionals should consider this relationship when following up and treating patients.

Endotheilum-specific deficiency of polycystin-1 promotes hypertension and cardiovascular disorders, and impairs arterio-venous fistula maturation

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent hereditary kidney disease and is generally due to mutations in PKD1 and PKD2, encoding polycystins 1 and 2. In ADPKD, hypertension and cardiovascular (CV) disorders are highly prevalent but their mechanisms are partially understood. The objective of this study was to determine whether hypertension and the CV disorders of ADPKD are a consequence of the endothelial deficiency in the polycystin complex, rather than to the kidney disease, as is currently believed. Since endothelial cells express the polycystin complex, where it plays a central role in the mechanotransduction of blood flow, we generated a murine model with inducible deletion of Pkd1 in endothelial cells (Cdh5-CreERT2; Pkd1fl/fl) to specifically determine the role of endothelial polycystin-1 in ADPKD. We analyzed the endothelial phenotype associated with Pkd1 deficiency, invasive and noninvasive blood pressure, vascular function on isolated vessels, and echocardiography. The impact on the development of a model of aorto-cava arterio-venous fistula and on the CV consequences of superimposed chronic kidney disease were analyzed to further establish the clinical relevance of our results. As expected, transgenic mice presented normal kidney structure and function. Endothelial deletion of Pkd1 induced endothelial dysfunction, as demonstrated by impaired flow-mediated dilatation of resistance arteries and impaired relaxation to acetylcholine, increased blood pressure and prevented the normal development of arterio-venous fistula. In experimental chronic kidney disease induced by subtotal nephrectomy, endothelial deletion of Pkd1 further aggravated endothelial dysfunction, vascular remodelling and heart hypertrophy ( Fig. 1 ). Altogether, this study provides the first in vivo demonstration that specific deletion of Pkd1 in endothelial cells promotes endothelial dysfunction and hypertension independently of kidney cysts and of impaired kidney function, impairs arterio-venous fistula development and potentiates the cardiovascular alterations associated with chronic kidney disease. It establishes the endothelium as a significant contributor to cardiovascular disease in ADPKD.

Potensi Minyak Herbal STIFA Pelita Mas Terhadap Kadar Ureum dan Kreatinin Tikus Kondisi Hiperglikemik

Utilization of natural preparations is a treatment carried out by the community with the aim of improving health status naturally. Traditional medicine has become an alternative for the community due to the relatively high cost of modern medicine. One of the diseases with a high financing burden is kidney disease, which is after heart and blood vessel disease. This study aims to determine the potential of traditional medicinal preparations of Herbal Oil STIFA Pelita Mas on the state of urea and creatinine concentrations in experimental animals, this research used white male rats divided into six treatments. Determination of urea and creatinine levels was carried out starting from days 1, 7, 14, 21 to 28, then normality and homogeneity tests were carried out, and parametric statistics were analyzed using the one-way ANOVA test. The results showed that the administration of STIFA Pelita Mas Herbal Oil in Formula 1, 2, and 3 had urea levels of 42.60 mg/dL, 28.64 mg/dL, and 51.46 mg/dL, respectively. The average values ​​of creatinine in Formula 1, 2, and 3 were 0.73 mg/dL, 0.63 mg/dL, and 0.92 mg/dL, respectively. The administration of Formula 2 was effective in reducing the concentration of urea and creatinine. Pelita Mas herbal oil preparation can be used as a medicine to improve kidney structure.